Nurzigma (pridopidine) / Prilenia, Ferrer International - LARVOL DELTA

First participant dosed in the PRECISE-HD trial of pridopidine (HDBuzz) - "PRECISE-HD is a global Phase 3 study that plans to enroll approximately 400 people aged 23-65 with early- to mid-stage HD across up to 75 clinical sites in North America and Europe....Researchers will measure whether pridopidine affects several aspects of HD, including overall disease progression (using the composite Unified Huntington’s Disease Rating Scale, or cUHDRS), day-to-day functioning, movement symptoms, thinking and cognition, speech and quality of life."

Trial status • CNS Disorders • Huntington's Disease

Pridopidine Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases. (PubMed, Neurol Int) - "Activation of S1R by pridopidine modulates calcium signaling and enhances anti-apoptotic activity. Collectively, available evidence suggests that pridopidine may improve motor outcomes and slow disease progression in Huntington's disease and amyotrophic lateral sclerosis, supporting its promise as a disease-modifying therapeutic strategy."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Huntington's Disease • Movement Disorders • DRD2

PRECISE-HD: Pridopidine Phase 3 Study in Huntington's Disease (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Prilenia | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders

Prilenia and Ferrer Announce Initiation of the Confirmatory PRECISE-HD Study of Pridopidine in Huntington’s Disease (Yahoo Finance) - "Recruitment has now commenced in the US, with other countries expected to follow on a rolling basis later in the year...Focused on further evaluating the efficacy and safety of pridopidine, an investigational medicinal product (taken as an oral capsule twice a day), and the generation of data to support registration, the confirmatory 400-participant randomized, double-blind, placebo-controlled PRECISE-HD study will assess the clinical impact of pridopidine on disease progression, functional capacity, motor function, cognition, speech and quality of life (QoL)."

Trial status • CNS Disorders • Huntington's Disease

PREVAiLS (Pridopidine Phase 3 Study To Evaluate Efficacy And Safety In ALS) A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study In ALS (ENCALS 2026) - "The study will also evaluate patient-reported outcomes, including communication. Conclusion PREVAiLS is a pivotal Phase 3 study aiming to confirm the potential clinical benefits on function and survival observed in the Phase 2 HEALEY ALS Platform Trial in participants with rapidly progressive ALS who are early in their disease course over a longer study period."

Clinical • P3 data • CNS Disorders • Huntington's Disease • Movement Disorders

PRECISE-HD: PRidopidine Phase 3 Study to Establish Clinical Impact and Safety in Huntington's Disease (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Prilenia

New P3 trial • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders

Beyond motor symptoms: efficacy of pharmacotherapies on motor, functional, and cognitive domains in Huntington's disease - a systematic review. (PubMed, Eur J Pharmacol) - "Dopaminergic, glutamatergic, and cholinergic drugs exhibit distinct efficacy profiles across various motor and non-motor UHDRS components. This positions them as therapeutic options for attenuating both the motor and non-motor symptoms in HD."

Clinical • Journal • Review • CNS Disorders • Cognitive Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders • Psychiatry

PL101-ALS301: Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS (PREVAiLS) (clinicaltrialsregister.eu) - P2/3 | N=420 | Recruiting | Sponsor: Ferrer Internacional S.A., Prilenia Therapeutics B.V. | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation. (PubMed, Int J Mol Sci) - "Co-treatment with the selective S1R antagonist, NE-100, attenuated these effects, supporting an S1R-mediated mechanism of action for pridopidine. Together, these results demonstrate that S1R activation by pridopidine mitigates ER-stress-induced mitochondrial dysfunction and cell loss in ALS-NPCs, resulting in enhanced survival of NPCs supporting the therapeutic potential of pridopidine in ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease • Metabolic Disorders • Movement Disorders • BAX • CASP3 • HSPA5

PL101-ALS301: Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS (PREVAiLS) (clinicaltrialsregister.eu) - P2/3 | N=420 | Not yet recruiting | Sponsor: Ferrer Internacional S.A., Prilenia Therapeutics B.V.

New P2/3 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

PL101-ALS301: Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS (PREVAiLS) (clinicaltrialsregister.eu) - P2/3 | N=395 | Not yet recruiting | Sponsor: Ferrer Internacional S.A., Prilenia Therapeutics B.V.

New P2/3 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Prilenia and Ferrer Announce First Participant Enrolled in the 'PREVAiLS' Phase 3 Study of Pridopidine in ALS (Businesswire) - "PREVAiLS is a pivotal, global, 500-participant Phase 3 study to evaluate efficacy and safety of pridopidine, an investigational drug, in slowing ALS progression (ALSFRS-R) in early, rapidly progressive participants....The PREVAiLS study is set to take place in up to 60 leading ALS treatment centers across 13 countries. 11 sites are already, or will imminently be, initiated, with recruitment at additional sites in the US, Canada, EU, UK and Israel expected to commence in the coming weeks and months."

Trial status • Amyotrophic Lateral Sclerosis

PREVAiLS: Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Prilenia | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

HEALEY ALS Platform Trial - Master Protocol (clinicaltrials.gov) - P2/3 | N=1500 | Recruiting | Sponsor: Merit E. Cudkowicz, MD | Active, not recruiting ➔ Recruiting | Trial primary completion date: Nov 2027 ➔ Jul 2027

Enrollment open • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Emerging neurobiological targets in psychiatric treatment. (PubMed, Eur Neuropsychopharmacol) - "Recent evidence suggests that sodium channel modulators, such as evenamide, may offer therapeutic benefits for treatment-resistant schizophrenia by stabilizing glutamatergic neurotransmission...Additionally, Sigma-1 receptor agonists, including Blarcamesine and Pridopidine, have shown neuroprotective and cognitive-enhancing properties, making them attractive candidates for psychiatric and neurodegenerative disorders. Orexin receptor antagonists, such as suvorexant and seltorexant, have potential in mood disorders and substance dependence, highlighting the broader therapeutic applications of targeting the orexinergic system...The identification of biomarkers for patient stratification will be critical in the hitherto elusive goal of developing precision medicine approaches. Targeted pharmacological interventions offer a path toward more effective, well-tolerated, and potentially individualized treatment options for patients with severe mental illness."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

PREVAiLS: Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS (clinicaltrials.gov) - P3 | N=500 | Not yet recruiting | Sponsor: Prilenia

New P3 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

HEALEY ALS Platform Trial - Master Protocol (clinicaltrials.gov) - P2/3 | N=1500 | Active, not recruiting | Sponsor: Merit E. Cudkowicz, MD | Trial completion date: Apr 2026 ➔ Aug 2028 | Trial primary completion date: Jul 2025 ➔ Nov 2027

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases. (PubMed, Pharmaceuticals (Basel)) - "Here, we review the experimental data demonstrating pridopidine's S1R-mediated neuroprotective effects. These findings underscore the therapeutic relevance of S1R activation and support further investigation of pridopidine for the treatment of different neurodegenerative diseases including ALS and HD."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Developmental Disorders • Huntington's Disease • Metabolic Disorders • Movement Disorders • Nephrology • Psychiatry • Rare Diseases

Prilenia and Ferrer Announce FDA Clearance to Start the “PREVAiLS” Pivotal Phase 3 Study with Pridopidine in ALS (Businesswire) - "Recruitment is planned to begin at the first US clinical trial sites in early 2026, with sites in Europe and other regions to follow, pending local clinical trial clearance...The study will consist of an initial 48-week double-blind placebo-controlled phase, randomized on a 3:2 (pridopidine:placebo) basis, followed by a 48-week open-label extension phase. The primary endpoint will be the change from baseline in ALSFRS-R adjusted for mortality at 48 weeks."

IND • New P3 trial • Amyotrophic Lateral Sclerosis

Huntington's disease clinical trials update: October 2025. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the launch of the phase II/III clinical trial of SKY-0515 from Skyhawk Therapeutics and the phase I/II clinical trial of SPK-10001 from Spark Therapeutics. Further updates include recent developments in Roche's tominersen programme within GENERATION HD2, progress with votoplam (PTC518) in PIVOT-HD by PTC Therapeutics and developments in the collaborative PTC Therapeutics/Novartis programme. We also report positive topline data from uniQure's phase I/II clinical trial of AMT-130 after 36 months of follow-up. We additionally discuss regulatory developments regarding pridopidine following the negative PROOF-HD study. Finally, we provide an updated listing of all registered and ongoing clinical trials in Huntington's disease."

Journal • Huntington's Disease • Movement Disorders

Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington’s Disease. (PubMed, Mol Neurobiol) - "The combination of these compounds may allow for lower efficacious doses leading to improved safety profiles and reduced off-target effects. This novel combinatorial approach, in which the S1R is activated while simultaneously inhibiting the S2R may prove to be a highly effective therapeutic strategy for HD and other neurodegenerative diseases."

Journal • CNS Disorders • Huntington's Disease • Retinal Disorders

Prilenia Therapeutics B.V. withdrew its application for the marketing authorisation of Nurzigma, a medicine intended for the treatment of adults with Huntington’s disease. (European Medicines Agency) - "The company withdrew the application on 7 November 2025."

European regulatory • Huntington's Disease

Pridopidine exerts neuroprotective effects through the activation of the sigma-1 receptor (S1R) by modulating ER stress in iPSC-derived neural progenitor cells (ALS-MND 2025) - "These findings highlight pridopidine's potential to enhance neuronal survival by mitigating ER stress, a key driver of ALS pathology. Given its ability to modulate fundamental disease mechanisms, pridopidine represents a promising therapeutic strategy for ALS."

CNS Disorders • Huntington's Disease • Movement Disorders • Psychiatry • BDNF • HSPA5

A planned phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pridopidine in participants with ALS (ALS-MND 2025) - "The HEALEY ALS Platform trial demonstrated a potential beneficial effect of pridopidine on ALS progression in a subgroup of rapidly progressing patients early in their disease course. A homogenous, rapidly progressive population is planned to be enrolled in order to determine a therapeutic effect within the limited timeframe of a clinical trial. Based on pridopidine's mechanism of action, it is anticipated that trial results will be extrapolatable to the broader population of people living with ALS."

Clinical • P3 data • CNS Disorders • Huntington's Disease • Movement Disorders

Prilenia and Ferrer plan to initiate a global confirmatory study of pridopidine in early-stage HD patients not taking ADMs - expected to commence in the first half of 2026. (Businesswire) - "In addition to the primary population, a small, proof-of-concept arm of patients taking low-dose ADMs (per label guidance) is also planned to be enrolled."

New trial • Huntington's Disease